Project Summary Marijuana is the most common drug of abuse among HIV-infected persons in the United States. Of the 1.2 million Americans living with HIV/AIDS, over half experience neurocognitive impairment, including deficits in executive control. Previous research has documented that marijuana and HIV independently disrupt functioning in the fronto-parietal executive control network of the brain, and white matter damage is an integral part of HIV-associated neuropathology. However, the interactions of marijuana and HIV on brain functioning and structure have not been well characterized. In this Imaging - Science Track Award for Research Transition (I/START) grant, we propose to combine multi-modal magnetic resonance imaging (MRI) and neuropsychological assessment to test whether marijuana use and HIV infection have synergistic effects on neurocognitive impairment, specifically in executive control functions, and how differences in brain function and structure relate to neurocognitive impairment. Using a case-control design, we will assess 60 adults across four study groups who differ on marijuana and HIV status (15/group). The specific aims are to examine white matter integrity using diffusion tensor imaging (DTI), functional connectivity using resting state functional MRI (RS-fMRI), and the relationship between neurocognitive impairment and these MRI data . Our multidisciplinary team, with expertise in clinical psychology, cognitive neuroscience, and MR physics, has extensive experience conducting patient-oriented research with HIV-infected drug users and is uniquely poised to successfully implement this innovative and clinically important project. The overarching goals of this research are to elucidate brain regions affected by marijuana and HIV that contribute to observed neurocognitive impairments in HIV-infected marijuana users. Results of this I/START grant will provide support for a subsequent R01 application to further investigate the role of marijuana in predicting neurocognitive decline in patients with early, middle, and advanced stages of HIV disease and test how frequency and chronicity of marijuana use moderate outcomes. This research has strong potential for translation to clinical practice (e.g., use of medical marijuana to treat HIV-related symptoms and integration of substance abuse treatment into HIV care) and will inform the development of neural biomarkers for early identification of neurocognitive decline in drug users, with the ultimate goal of reducing HIV-related morbidity and mortality in the many HIV-infected persons who abuse drugs.